Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection
Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection
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Slc6a13 缺乏促进肠道细菌感染期间 Th17 反应
DOI：
10.1038/s41385-018-0111-7
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发表时间：
2019-02-01
影响因子：
8
通讯作者：
Yin, Yulong
中科院分区：
文献类型：
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作者：
Ren, Wenkai;Liao, Yuexia;Yin, Yulong
γ-氨基丁酸 (GABA) 能系统决定免疫细胞的激活和功能。本研究旨在探讨GABA转运蛋白(GAT)-2对Th17细胞分化的调控作用。在这里，我们发现与初始 T 细胞相比，Th17 细胞显示出更高丰度的 GAT-2，并且具有独特的细胞代谢特征，例如 GABA 分流途径。 GAT-2 缺陷对幼稚 T 细胞的代谢特征几乎没有影响，但损害了 Th17 细胞中的 GABA 摄取和 GABA 分流途径。 GAT-2缺陷对T细胞发育和外周T细胞稳态影响不大；然而，它的缺陷却促进了体外Th17细胞的分化。从机制上讲，GAT-2 缺陷通过激活 GABA-mTOR 信号传导促进 Th17 细胞的分化。在肠道感染和炎症的小鼠模型中，GAT-2 缺陷促进了 Th17 反应。总的来说，GAT-2 缺陷通过激活 GABA-mTOR 信号传导促进 Th17 细胞反应。
The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naïve T cells. GAT-2 deficiency had little effect on the metabolic signature in naïve T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA-mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA-mTOR signaling.